Panax notoginseng-Bletilla striata ameliorates reflux esophagitis by modulating NLRP3 inflammasomes and p38 MAPK pathway

三七-白及通过调节NLRP3炎症小体和p38 MAPK通路改善反流性食管炎

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Abstract

This study was to investigate the therapeutic effect of Panax notoginseng-Bletilla striata (PN-BS) in reflux esophagitis (RE) and its molecular mechanism. Using the '4.2 mm pyloric clamp + 2/3 fundoplication' method, a rat model of RE was developed. RE cell model was established by exposing HET-1 A (esophageal epithelial cells) to bile salt. Esophageal mucosal injury was observed by HE staining, and epithelial barrier dysfunction was assessed using Toluidine blue staining. HET-1 A cell viability was measured by CCK-8. Inflammatory factors in tissues and cells were detected by enzyme-linked immunosorbent assay. Claudin-4, Claudin-5, NLRP3, cleaved-caspase-1, p-p38 MAPK, and p38 MAPK protein levels were detected by Western blot. PN-BS attenuated esophageal mucosal injury and inflammation and improved esophageal barrier dysfunction in RE rats. Panax notoginseng saponins (PNS, the main active ingredient of PN) and Bletilla striata polysaccharides (BSP, the main active ingredient of BS) attenuated acid and bile salt-induced esophageal barrier dysfunction. PNS and BSP inhibited NLRP3 inflammasomes and p38 MAPK pathway activation. An inhibitor of NLRP3 inflammasomes (MCC950) or an inhibitor of the p38 MAPK pathway (SB203580) further enhanced the ameliorative effects of PNS and BSP. PN-BS reduces esophageal barrier dysfunction by inhibiting the activation of NLRP3 inflammasomes and p38 MAPK pathway, thereby improving RE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00858-9.

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